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首页> 外文期刊>Current Drug Targets >Di / tri-Peptide Transporters as Drug Delivery Targets: Regulation of Transport Under Physiological and Patho-physiological Conditions
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Di / tri-Peptide Transporters as Drug Delivery Targets: Regulation of Transport Under Physiological and Patho-physiological Conditions

机译：二/三肽转运蛋白作为药物递送目标：在生理和病理生理条件下的运输调控

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摘要

Two human di / tri-peptide transporters, hPepT1 and hPepT2 have been identified and functionally characterized. In the small intestine hPepT1 is exclusively expressed, whereas both PepT1 and PepT2 are expressed in the proximal tubule. The transport via di / tri-peptide transporters is proton-dependent, and the transporters thus belong to the Proton-dependent Oligopeptide Transporter (POT)-family. The transporters are not drug targets per se, however due to their uniquely broad substrate specificity; they have proved to be relevant drug targets at the level of drug transport. Drug molecules such as oral active β-lactam antibiotics, bestatin, prodrugs of aciclovir and ganciclovir have oral bioavailabilities, which largely are a result of their interaction with PepT1. In the last few years an increasing number of studies concerned with regulation of di / tri-peptide transporter capacity have appeared. Studies on receptor-mediated regulation has shown that both PepT1 and PepT2 is down-regulated by long-term exposure to epidermal growth factor (EGF) due to a decreased gene transcription. PepT1-mediated transport is upregulated by certain substrates and in response to fasting and starvation at the level of increased gene transcription. PepT1-mediated transport is up-regulated by short-term exposure to receptor agonists such as EGF, insulin, leptin, and clonidine, and down-regulated by VIP. Overall, the regulation of di / tri-peptide transport may be contributed to 1) changes in apical proton-motive force 2) recruitment of di / tri-peptide transporters from vesicular storages 3) changes in gene transcription / mRNA stability. The aim of the present review is to discuss physiological, patho-physiological and druginduced regulation of di / tri-peptide transporter mediated transport.
机译：已经鉴定出两种人的二/三肽转运蛋白hPepT1和hPepT2。在小肠中，hPepT1仅表达，而PepT1和PepT2均在近端小管中表达。通过二/三肽转运蛋白的转运是质子依赖性的，因此转运蛋白属于质子依赖性寡肽转运蛋白（POT）家族。转运蛋白本身并不是药物靶标，但是由于其独特的广泛底物特异性；在药物运输方面，它们已被证明是相关的药物靶标。口服活性β-内酰胺类抗生素，bestatin，阿昔洛韦和更昔洛韦的前药等药物分子具有口服生物利用度，这在很大程度上是由于它们与PepT1相互作用所致。在最近几年中，关于调节二/三肽转运蛋白能力的研究越来越多。受体介导的调控研究表明，由于基因转录减少，长期暴露于表皮生长因子（EGF）会降低PepT1和PepT2的表达。 PepT1介导的转运受某些底物上调，并在空腹和饥饿时以增加的基因转录水平上调。 PepT1介导的转运通过短期暴露于受体激动剂（如EGF，胰岛素，瘦素和可乐定）而上调，而VIP则下调。总体而言，二肽/三肽转运的调节可能与以下因素有关：1）顶质子动力的改变2）从水泡贮藏中募集二肽/三肽转运蛋白3）基因转录/ mRNA稳定性的改变。本综述的目的是讨论二肽/三肽转运蛋白介导的转运的生理，病理生理和药物诱导的调节。

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